Policy challenges and the reform of postal savings in Japan

This paper discusses the current policy challenges to the existence of Japan's postal saving system, the main repository for Japan's household savings. Some critics have erroneously conflated the investment function of mobilized funds that occurred under the government's managed by the Ministry of Finance, with the collection mechanism managed separately by the Ministry of Posts. Critically reviewed are the efficacy and wisdom of the search for market-oriented investment policies in view of the public's real fears for the safety of their savings; current proposals to privatize, not only the postal savings system but also the post delivery system itself and the potential loss of essential services to rural populations

Multinational banks and development finance

Financial market recommendations for less industrialized economies, particularly in the wake of the recent financial crises, have included a push for more international financial competition. The entry of multinational banks (MNBs) into developing economies is supposed to create more market discipline for domestic banks, thus making them more efficient, and enhancing financial stability. Using data from the BIS and the IMF, we look at the determinants of MNB presence, at MNB activities, and their impact on credit supply and on financial stability. With respect to the determinants of MNB presence, we find that lower asset prices, a ready market and competition with other MNBs matter more than economic fundamentals of the host economy. In line with these results, MNBs focus their activities predominantly on serving MNCs, and on providing services that domestic banks cannot offer to domestic corporations, and high net worth individuals. Thus, we also find that domestic banks lower their total credit exposure by reducing their commercial loans in response to increased competition, particularly in serving MNCs, domestic corporations, or high net worth individuals, which may lead to real implications for less industrialized economies, particularly lower business investment. --

Japanese banking in the United States: From transient advantage to strategic failure

Japanese banks instantly became major players in world financial markets when the 1985 Plaza Accord doubled the value of the yen. Access to cheap capital and long-term relationships with Japanese firms doing business abroad allowed them to undercut overseas rivals and achieve early success. However this quick-term overseas strategy lacked a defined long-term outlook. Based upon the author's interviews with 61 Japanese bankers, this paper examines the failure of Japanese banks to create and sustain competitive advantage. Their lack of "soft" resources, such as international experience, knowledge about local markets, and management expertise, have all contributed to their recent retreat

Multinational banks and development finance

Financial market recommendations for less industrialized economies, particularly in the wake of the recent financial crises, have included a push for more international financial competition. The entry of multinational banks (MNBs) into developing economies is supposed to create more market discipline for domestic banks, thus making them more efficient, and enhancing financial stability. Using data from the BIS and the IMF, we look at the determinants of MNB presence, at MNB activities, and their impact on credit supply and on financial stability. With respect to the determinants of MNB presence, we find that lower asset prices, a ready market and competition with other MNBs matter more than economic fundamentals of the host economy. In line with these results, MNBs focus their activities predominantly on serving MNCs, and on providing services that domestic banks cannot offer to domestic corporations, and high net worth individuals. Thus, we also find that domestic banks lower their total credit exposure by reducing their commercial loans in response to increased competition, particularly in serving MNCs, domestic corporations, or high net worth individuals, which may lead to real implications for less industrialized economies, particularly lower business investment

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q₁ = 4.9 % and q₃ = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data

Feasibility of Long-Term Patient Self-Reporting of Toxicities From Home via the Internet During Routine Chemotherapy

Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits

Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3

Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups

Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic.

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.The COG-UK Consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. O.G.P. was supported by the Oxford Martin School. J.T.M., R.M.C., N.J.L., and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z – ARTIC network). D.L.R. acknowledges the support of the MRC (MC_UU_12014/12) and the Wellcome Trust (220977/Z/20/Z). E.S. and A.R. are supported by the European Research Council (grant agreement no. 725422 – ReservoirDOCS). T.R.C. and N.J.L. acknowledge the support of the MRC, which provided the funding for the MRC CLIMB infrastructure used to analyze, store, and share the UK sequencing dataset (MR/L015080/1 and MR/T030062/1). The samples sequenced in Wales were sequenced partly using funding provided by the Welsh Government

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

<p>Abstract</p> <p>Background</p> <p>The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silico<it/>model of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.</p> <p>Results</p> <p>The in silico<it/>SBML model reflected the in vivo<it/>aging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.</p> <p>Conclusion</p> <p>Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitro<it/>and in vivo<it/>studies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.</p